The National Academy of Sciences - National Research Council Registry of aging twin veterans ("the Registry") contains 6,000 living pairs of white male twins who will be aged 68-80 in 1996-97. This extensively revised application proposes studies in the Registry that, combined with work to date, will yield 130 twin pairs with Alzheimer's disease (AD). That population-based panel will enable the continued investigation of three broad aims: 1) evaluation of genetic causes of AD by contrasting the similarity of onsets within monozygotic (MZ) and dizygotic (DZ) pairs, and within age-matched pairs of unrelated individuals; 2) characterization of the environmental contribution to variability of onset of AD; (for example, variability of onset within MZ pairs defines the maximum degree to which environmental influences can modify the onset of AD); and 3) identification of specific factors associated with accelerated onset of AD, using the co-twin control method. The research will capitalize upon recent developments in the genetics of AD. Genotype at the locus for apolipoprotein E (APOE) influences both liability to AD and its timing of onset. Other similar genetic systems may soon be identified. Such findings enable the incorporation of refinements into the classical twin paradigm of investigating broad (but heterogeneous) genetic and environmental influences. Thus, the investigators state that one can not only estimate the heritability of AD in general, but also undertake partitioned analyses to estimate the phenotypic variance to genotypes at APOE or other marker systems, as these are identified, and to still other (unknown) genes that predispose to AD. Several MZ twin pairs have been described with widely divergent onsets of AD. Environmental factors may therefore alter the onset, and hence the population risk, of some genetically defined forms of AD. This study will analyze the environmental contribution to variability of onset, and will characterize the divergence in onset within sets of genetically matched individuals. It will also employ the co-twin control method to seek the specific environmental factors that may be responsible for this variation. Because the AD cases here will typically have experienced a relatively early onset (given their genotype), the investigators will concentrate on factors that accelerate the onset of AD. Reduction in population exposure to such factors could result in a dramatic decrease in the public health burden of AD. The investigators state that a population-based twin design remains the ideal approach to these sorts of investigations, but the cost of such studies is a concern. They further state that alterations to the current work plan have resulted in a budget reduction of 19.2%, as compared wit the prior application.